The objective of the proposed project is the characterization of the properties of the different types of serotonin (5-hydroxytryptamine, 5-HT) receptors in the mammalian central nervous system. The first part of this involves the use of in vitro binding assays utilizing various ligands, such as 3H-5-HT, 3H-spiperone, and 3H-LSD which are thought to label certain populations of serotonin receptors. Secondly, the properties of these putative 5-HT receptors will be compared to those which regulate adenylate cyclase activity (both high- and los-sensitivity systems) and those which regulate the release of 5-HT itself as measured by in vitro techniques. The third part will be the comparison of the receptors measured in the first two parts with functional 5-HT receptors which produce physiological or behavioral chanes in vivo. This will include examination of the 5-HT receptors which modulate release of prolactin and thyrotropin, the receptors involved in the so-called 5-HT behavioral syndrome (which has been suggested as a possible model for amphetamine-induced paranoid psychosis ora paranoid schizophrenia), a possible model for amphetamine-induced paranoid psychosis or paranoid schizophrenia), and those involved in the rat-rotational model (a system praoposed for the evaluation of the possible role of 5-HT in Parkinson's disease). The major emphasis of this work will be the pharmacological characterization of these sites in an attempt to determine the strurctural aequirements of compounds foir discrimination between different types of serotonin receptors, although the in vitro studies will also be used to characterize and compare the receptors on the basis of their subcellular distributions, their cellular localization, and their regional distributions. Once these groups of receptors are classified and characterized, it is hoped that more specific drugs can be designed for affecting selected gaoups of 5-HT receptors so that the action of 5-HT in the central nervous system can be more carefully studied. It is hoped that such information can eventurally be used foar the design of new, more effective therapeutic agents foar the treatment of behavioral or mental disorders that are thought to be linked to abnormal serotonergic function.